Ring-opening polymerization (ROP) is an addition polymerization where the terminal end of a polymer acts as a reactive center and cyclic monomers join to form a larger polymer chain. In the case of a polylactide, an alkoxide of a metal having d orbitals, such as, aluminum or tin, is considered an effective initiator for ROP of lactides (see, e.g., Biopolymers from Renewable Resources, Hartmann et al. (eds.), 1998, Spring-Verlag, Berlin, herein incorporated by reference in entirety). Metal-free, purely organic catalysts have been reported using either tertiary amines or phosphines as nucleophilic transesterification catalysts (see, e.g., Nederberg et al., Agnew Chem Int Ed (2001) 40:2712; Nederberg et al., Chem Comm (2001) 2006; and Kamber et al., Chem Rev (2007) 107:5813, herein incorporated by reference in entirety). A more recent class of organocatalysts for ROP are the N-heterocyclic carbenes (NHCs) which have been studied in the polymerization of ε-caprolactone to provide polycaprolactones with controlled molecular weight and low polydispersity (see, e.g., Kamber et al., Macromolecules (2009) 42 (5):1634, herein incorporated by reference in entirety). All those processes rely on stringent anhydrous conditions and many involve reactions under pressure with solvent.
Lactide may be copolymerized with a number of different monomers including other lactone monomers, such as, glycolide and caprolactone. Block copolymers of polycaprolactone and polylactide may be prepared in two ways: first, via a sequential addition of the required monomer to the living growing chain end of the first monomer; and the second is by making a prepolymer with a hydroxyl end group to which the second monomer may be added in the presence of a catalyst (see, e.g., Bero et al., Polym Bull (1993) 21:9, and Veld et al., J Polym Sci Part A Polym Chem (1997) 35:219, herein incorporated by reference in entirety).
The reactivity of lactone monomers is much lower than that of lactide monomers which generally proscribes one-pot processes.
A one-pot, neat, organocatalytic ROP process for generating polymers and copolymers, which can be functionalized, was developed. Such polymers and copolymers can be tuned to promote self-assembly into organic biodegradable nanoparticles. However, some compositions, such as those containing a polylactide (PLA) block at the chain end, are susceptible to premature degradation through ring-closing reactions initiated at the hydroxyl terminus.
Thus, what is needed is a method that stabilizes the hydroxyl chain end to provide greater hydrolytic stability, including introducing additional functionalities for particular uses.